A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL

NCT02514083 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 15017215-H-0172
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given in cycles 3 and 4. The primary efficacy endpoint is the rate of complete response after 6 cycles or 24 weeks. The primary safety endpoint is the rate of treatment discontinuation after 6 cycles or 24 weeks.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Bruton's tyrosine kinase inhibitor; Fludarabine; Immune modulation

Outcome Measures

Primary Outcomes (2)

• Rate of Complete Response at 24 Weeks

  Rate of complete response at 24 weeks or after 6 cycles. Response assessment was conducted according to the guidelines from the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL).

  24 weeks

• Rate of Treatment Discontinuation Within the First 24 Weeks

  Rate of treatment discontinuation within the first 24 weeks or 6 cycles due to intolerable side effects from study therapy

  24 weeks

Study Arms (1)

Ibrutinib and short-course fludarabine

EXPERIMENTAL

* Ibrutinib 420 mg PO daily for the duration of the study * Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Drug: Ibrutinib; Drug: Fludarabine

Interventions

Ibrutinib DRUG

Ibrutinib 420mg PO daily for the duration of the study.

Also known as: Imbruvica

Ibrutinib and short-course fludarabine

Fludarabine DRUG

Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Also known as: Fludara

Ibrutinib and short-course fludarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women with histologically confirmed disease as defined by the following:
• CLL: clonal B-lymphocytosis greater than or equal to 5,000 cells/microL .
• SLL: lymphadenopathy with the tissue morphology of CLL but that are not leukemic, \< 5,000 cells/microL.
• Immunophenotypic profile or immunohistochemistry read by an expert pathologist as consistent with CLL. This will include CD5, CD19, and CD20 expression by the CLL cells typically also with CD23 expression, but CD23 negative cases may be included if there is an absence of t(11;14).
• Active disease as defined by at least one of the following (IWCLL consensus criteria):
• Weight loss greater than or equal to 10% within the previous 6 months
• Extreme fatigue
• Fevers of greater than 100.5 F for greater than or equal to 2 weeks without evidence of infection
• Night sweats for more than one month without evidence of infection
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• Massive or progressive splenomegaly
• Massive nodes or clusters or progressive lymphadenopathy
• Progressive lymphocytosis with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months
• Treatment naive CLL/SLL patients
• Treatment-naive CLL indicates no prior anti-CLL therapy. Anti-CLL therapy includes chemotherapies, monoclonal antibodies, and targeted agents with known or reasonably expected anti-leukemic activity.

You may not qualify if:

• Transformed CLL, including Hodgkin and non-Hodgkin lymphoma
• Active autoimmune hemolytic anemia or thrombocytopenia
• Known bleeding disorders
• Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper limit of normal unless due to Gilbert's disease, aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to 2.5 times institutional upper limit of normal unless due to infiltration of liver, Child-Pugh class B or C
• Impaired renal function: estimated glomerular filtration rate (GFR) \< 30ml/min/1.73m(2) based on CKD-EPI
• Life-threatening illness, medical condition or organ system dysfunction which, in the investigators opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib and fludarabine, or put the study outcomes at undue risk
• Concomitant immunomodulatory therapy, chemotherapy, radiotherapy or experimental therapy
• Active Hepatitis B or Hepatitis C infection
• HIV infection
• Female patients who are currently in pregnancy, or unwilling to use acceptable methods of contraception or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol.
• Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.
• Unable to understand the investigational nature of the study or give informed consent.
• Individuals \< 18 years old
• Known hypersensitivity to any component of ibrutinib or fludarabine
• Requires concomitant anticoagulation with Coumadin (warfarin) or other vitamin K antagonists.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016 Oct 13;128(15):1940-1943. doi: 10.1182/blood-2016-06-722991. Epub 2016 Aug 8.

  PMID: 27503501 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Inhye Ahn, M.D.
• Organization: National Heart Lung and Blood Institute (NHLBI)

inhye.ahn@nih.gov

301-827-1203

Study Officials

• Andy Itsara, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2015
• First Posted: August 3, 2015
• Study Start: December 9, 2015
• Primary Completion: October 2, 2019
• Study Completion (Estimated): October 23, 2034
• Last Updated: April 14, 2026
• Results First Posted: October 8, 2020

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)